Our understanding of Noise-Induced Hearing Loss is rather rudimentary, despite the importance of this problem to human occupational and recreational health. The damage is permanent because mammals cannot regenerate their auditory hair cells once they die. Studies of the underlying causes of noise-induced hearing loss have focused on mechanical damage to cells, and molecular studies centered around oxidative damage and cytoskeletal disruptions. Mammalian studies are challenged by difficult access to the inner ear inside the temporal bone, and expensive animal care costs. In this proposal we seek to capitalize on the genetic model organism, Drosophila, to systematically characterize gene expression changes induced by acute or chronic over-exposure to sound. Our preliminary results show that there are strong immediate effects on auditory function after acute exposure. We propose first to study the immediate and longer-term morphological and physiological consequences of these forms of noise trauma. Second, we will identify genome-wide responses to acoustic stress using microarray analysis. These studies will provide insight into possible pathways through which to increase resistance to noise damage as a preventative measure, or to reduce the deleterious effects of noise damage after the fact as a therapeutic measure. They will also inform the individual genetic differences in susceptibility to noise damage. PUBLIC HEALTH RELEVANCE: Over-exposure to noise is a serious problem in today's industrial and technological world, especially with increasing age structure in human populations. The proposed project uses the genetic model organism Drosophila to investigate functional and structural consequences to the auditory organ upon acute or chronic over-exposure to sound, and to understand gene expression changes evoked by this treatment. The results of our studies will facilitate identification of putative preventative and therapeutic targets for human noise-induced hearing loss and age-related hearing loss.